Multi-Analyte Liquid Biopsies for Molecular Pathway Guided Personalized Treatment Selection in Advanced Refractory Cancers: A Clinical Utility Pilot Study

Abstract

Prior attempts at personalizing anticancer treatments based on univariate tumor profiling (single gene variant) for selection of monotherapy with targeted agents (single drug) have generally yielded poor response rates. We report findings from the LIQUID IMPACT pilot trial where Multi-analyte Liquid Biopsy (MLB) profiling of circulating tumor analytes in peripheral blood was used to inform selection of personalized combination regimens in advanced refractory cancers. Among the 43 patients evaluable as per study protocol, 34 had targetable pathway activations. Partial Response (PR) was observed in 14 (41.1%) of the 34 patients with signaling pathway activation, including 5 (50%) of 10 cases with mTOR activation, 8 (44.4%) of 18 cases with activation of angiogenesis and 4 (50.0%) of 8 cases with EGFR / ERBB2 activation. PR was not reported among the 9 cases with no detectable pathway activation. Toxicities were manageable and there were no treatment related deaths. The study findings suggest that MLB may be able to inform safe and efficacious combination regimens in patients with advanced refractory cancers.